CN109942639B - Preparation method of high-purity fructose diphosphate magnesium - Google Patents
Preparation method of high-purity fructose diphosphate magnesium Download PDFInfo
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- CN109942639B CN109942639B CN201910217958.9A CN201910217958A CN109942639B CN 109942639 B CN109942639 B CN 109942639B CN 201910217958 A CN201910217958 A CN 201910217958A CN 109942639 B CN109942639 B CN 109942639B
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Abstract
The invention discloses a preparation method of fructose diphosphate magnesium, which comprises the following steps: enabling fructose-1,6-diphosphate and a composition containing nano magnesium hydroxide to react in water to generate fructose magnesium diphosphate, wherein the feeding molar ratio of the fructose-1,6-diphosphate to the magnesium in the nano magnesium hydroxide is controlled to be 1.01-1.03: 1; the method can obtain the product with high yield and high purity, has simple process and is suitable for industrial production.
Description
Technical Field
The invention belongs to the field of chemical medicine, particularly relates to fructose-1,6-diphosphate and derivatives thereof, and particularly relates to a preparation method of fructose magnesium diphosphate.
Background
Fructose-1,6-diphosphate (FDP) was identified as an important intermediate in sugar metabolism as early as 30 in the 20 th century. The derivative fructose diphosphate magnesium (structure is shown as formula I, and magnesium salt) prepared from fructose-1,6-diphosphate is an effective medicine for treating myocardial ischemic diseases and cerebral ischemic diseases;
for example, Chinese patent CN95100068.3 discloses a process for preparing fructose diphosphate magnesium, which comprises, using sucrose, disodium hydrogen phosphate and yeast as raw materials, anaerobic fermentation of microorganism at 41 + -2 deg.C for 4 hours, testing with magnesium mixture to confirm complete phosphorylation, converting bismuth nitrate into bismuth salt precipitate, and finally converting magnesium chloride into fructose diphosphate magnesium, which is shown in the examples, we can know that the yield is very low about 9%, and the purity is not ideal after repeated experiments by the applicant, and the fructose diphosphate magnesium has unexpected special activity as a medicine for treating myocardial infarction, and pharmacological tests show that when myocardial ischemia occurs, the injection of fructose diphosphate magnesium can make the myocardial ischemia not suffer from the subsequent ischemic injury, which is medically known to have a pre-prepared effect, and does not differentiate the age of patients, therefore, it is highly desirable to find a way to solve the above problems, and further to enable the preparation of magnesium fructose diphosphate for industrial production and large-scale application in the medical field.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects in the prior art, and provide an improved method for preparing fructose diphosphate magnesium, which can obtain products with high yield and high purity, has simple process and is suitable for industrial production.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a preparation method of fructose diphosphate magnesium comprises the following steps: reacting fructose-1,6-diphosphate with a composition containing nano-magnesium hydroxide in water to generate the fructose-magnesium diphosphate, wherein the feeding molar ratio of the fructose-1,6-diphosphate to the magnesium in the nano-magnesium hydroxide is controlled to be 1.01-1.03: 1.
According to some preferred aspects of the invention, in the preparation method, the feeding molar ratio of the fructose-1, 6-diphosphonic acid to the magnesium in the nano magnesium hydroxide is controlled to be 1.01-1.02: 1.
According to some specific and preferred aspects of the invention, the specific embodiments of the preparation of magnesium fructose diphosphate are: adding the composition containing the nano magnesium hydroxide into the aqueous solution of the fructose-1,6-diphosphate in batches for reaction.
According to some preferred aspects of the present invention, the composition further comprises a thickener and water, and the composition is prepared by mixing and stirring nano magnesium hydroxide, water and the thickener for preventing the nano magnesium hydroxide from agglomerating.
According to some preferred aspects of the invention, the feed amount of the thickener is 0.1-1% by mass of the composition.
According to some preferred aspects of the invention, the feed mass ratio of the thickener to the nano magnesium hydroxide is 0.1-0.5: 1.
According to some preferred aspects of the invention, the thickener consists of gum arabic and hydroxypropyl starch ether in a mass ratio of 1: 1-2.
In some embodiments of the invention, the method of preparing further comprises: and filtering the reaction mixture obtained after the reaction to obtain a crude product, mixing the crude product with an ethanol solution, stirring, filtering, adding the ethanol solution, stirring, crystallizing, filtering, and drying to obtain the fructose magnesium diphosphate.
In some embodiments of the invention, the temperature of the reaction is allowed to range from 20 to 35 ℃.
Due to the adoption of the technical scheme, compared with the prior art, the invention has the following advantages:
the fructose diphosphate magnesium is prepared by reacting nano-sized magnesium hydroxide with fructose-1,6-diphosphate, so that the preparation process is simple and easy to implement, excellent yield and purity can be obtained, the defects in the prior art are overcome, and the fructose diphosphate magnesium can be industrially produced, so that the therapeutic effect of the fructose diphosphate magnesium can be fully exerted in medical treatment.
Detailed Description
The above-described scheme is further illustrated below with reference to specific examples; it is to be understood that these embodiments are provided to illustrate the general principles, essential features and advantages of the present invention, and the present invention is not limited in scope by the following embodiments; the implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not indicated are generally the conditions in routine experiments.
In the following, all starting materials are essentially obtained commercially or prepared by conventional methods in the art, unless otherwise specified.
EXAMPLE 1 preparation of magnesium fructose diphosphate
(1) Preparing a fructose-1, 6-diphosphonic acid aqueous solution: adding fructose-1,6-diphosphate (1.01mol) into water (4L) and stirring to prepare a fructose-1,6-diphosphate aqueous solution;
(2) preparing a composition containing nano magnesium hydroxide: mixing nano magnesium hydroxide (1mol), water (6L), Arabic gum (5.8g) and hydroxypropyl starch ether (5.8g), and stirring to obtain the final product;
(3) and (2) quantitatively adding the composition containing the nano magnesium hydroxide prepared in the step (2) into the fructose-1, 6-diphosphonic acid aqueous solution prepared in the step (1) in batches for 10 times, reacting at room temperature, filtering a reaction mixture obtained after the reaction by using a 0.22-micrometer filter membrane to obtain a crude product, mixing the crude product with an ethanol aqueous solution with the mass fraction of 95%, stirring, filtering, adding an ethanol aqueous solution with the mass fraction of 95%, stirring, crystallizing, filtering and drying to obtain 329.7g of fructose diphosphate magnesium, wherein the yield is about 91% and the purity is about 98.3%.
Example 2 preparation of magnesium fructose diphosphate
(1) Preparing a fructose-1, 6-diphosphonic acid aqueous solution: adding fructose-1,6-diphosphate (1.02mol) into water (4L) and stirring to prepare a fructose-1,6-diphosphate aqueous solution;
(2) preparing a composition containing nano magnesium hydroxide: mixing nano magnesium hydroxide (1mol), water (5L), Arabic gum (11.7g) and hydroxypropyl starch ether (11.7g), and stirring to obtain the final product;
(3) quantitatively adding the composition containing the nano magnesium hydroxide prepared in the step (2) into the fructose-1, 6-diphosphonic acid aqueous solution prepared in the step (1) in batches for 20 times, reacting at room temperature, filtering a reaction mixture obtained after the reaction by using a 0.22-micrometer filter membrane to obtain a crude product, mixing the crude product with an ethanol aqueous solution with the mass fraction of 95%, stirring, filtering, adding an ethanol aqueous solution with the mass fraction of 95%, stirring, crystallizing, filtering and drying to obtain 323.2g of fructose diphosphate magnesium, wherein the yield is about 89.2% and the purity is about 97.7%.
Example 3 preparation of magnesium fructose diphosphate
(1) Preparing a fructose-1, 6-diphosphonic acid aqueous solution: adding fructose-1,6-diphosphate (2.02mol) into water (8L) and stirring to prepare a fructose-1,6-diphosphate aqueous solution;
(2) preparing a composition containing nano magnesium hydroxide: mixing nano magnesium hydroxide (2mol), water (30L), Arabic gum (23g) and hydroxypropyl starch ether (23g), and stirring to obtain the product;
(3) quantitatively adding the composition containing the nano magnesium hydroxide prepared in the step (2) into the fructose-1, 6-diphosphonic acid aqueous solution prepared in the step (1) in 10 batches, reacting at room temperature, filtering a reaction mixture obtained after the reaction by using a 0.22 mu m micron filter membrane to obtain a crude product, mixing the crude product with 95% by mass of ethanol aqueous solution, stirring, filtering, adding 95% by mass of ethanol aqueous solution, stirring, crystallizing, filtering and drying to obtain 670.2g of fructose diphosphate magnesium, wherein the yield is about 92.5% and the purity is about 98.5%.
Comparative example 1
The procedure is essentially the same as in example 1, except that 265.2g of fructose diphosphate was obtained in 73.2% yield and 96.3% purity by replacing the composition containing nano-sized magnesium hydroxide with conventional powdered magnesium hydroxide.
Comparative example 2
The procedure of example 1 was repeated except that 288.4g of fructose diphosphate was obtained in 79.6% yield and 97.6% purity without adding a thickener.
The above embodiments are merely illustrative of the technical concept and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the content of the present invention and implement the invention, and not to limit the scope of the invention, and all equivalent changes or modifications made according to the spirit of the present invention should be covered by the scope of the present invention.
Claims (4)
1. The preparation method of fructose diphosphate magnesium is characterized by comprising the following steps: reacting fructose-1,6-diphosphate with a composition containing nano-magnesium hydroxide in water to generate fructose magnesium diphosphate, wherein the feeding molar ratio of the fructose-1,6-diphosphate to the magnesium in the nano-magnesium hydroxide is controlled to be 1.01-1.03: 1;
wherein the composition also comprises a thickening agent and water, and the composition is prepared by mixing and stirring nano magnesium hydroxide, water and the thickening agent for preventing the nano magnesium hydroxide from agglomerating;
the specific implementation mode for preparing the fructose diphosphate magnesium is as follows: adding the composition containing the nano magnesium hydroxide into the aqueous solution of fructose-1,6-diphosphate in batches for reaction;
the feeding amount of the thickening agent accounts for 0.1-1% of the mass percentage of the composition; the feeding mass ratio of the thickening agent to the nano magnesium hydroxide is 0.1-0.5: 1;
the thickening agent is composed of Arabic gum and hydroxypropyl starch ether in a mass ratio of 1: 1-2.
2. The method for preparing magnesium fructose diphosphate according to claim 1, wherein the molar ratio of fructose-1,6-diphosphate to magnesium in the nano-sized magnesium hydroxide is controlled to be 1.01-1.02: 1.
3. The method of preparing magnesium fructose diphosphate according to claim 1, further comprising: and filtering the reaction mixture obtained after the reaction to obtain a crude product, mixing the crude product with an ethanol solution, stirring, filtering, adding the ethanol solution, stirring, crystallizing, filtering, and drying to obtain the fructose magnesium diphosphate.
4. The method for producing magnesium fructose diphosphate according to claim 1, wherein the temperature of the reaction is set to 20 to 35 ℃.
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| CN1042953C (en) * | 1995-07-10 | 1999-04-14 | 暨南大学 | Magnesium hexose diphosphate and its production |
| CN1172944C (en) * | 2000-01-17 | 2004-10-27 | 欧阳平凯 | Preparation of magnesium fructose-1,6-diphosphate |
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